Generation of bone is a challenge many scientists in the fields of tissue engineering have been facing with not much success. Bone generation depends, to a great extent, on bioactive scaffolds and on osteoprogenitors. A number of different synthetic calcium based bone graft substitutes (BGS) are currently available for clinical use. Although these materials have demonstrated clinical effectiveness in terms of defect fill, predictability for high rate of success in terms of regeneration has not yet been achieved. Several biomaterials have been developed to fill and reconstruct bone defects: natural coral, bovine porous demineralized bone, human demineralized bone matrix (DBM), bioactive glass ceramics and calcium phosphate ceramics such as hydroxyapatite, β-tricalcium phosphate or biphasic calcium phosphate [1,2,3]. These materials are biocompatible and osteoconductive, guiding bone tissue from the edges toward the center of the defect. Some materials of biological origin, such as bovine bone (xenografts), demineralized bone matrix (DBM) and allogenic bone grafts may have osteoinductive properties. However, biologically-derived organic materials present a risk of an immunological response and disease transfer, and the manufacturer must apply viral inactivation. Although many types of materials are currently available for bone repair, they are being continuously optimized with regard to their chemistry, architecture, and mechanical properties to more closely mimic the properties of bone itself. Among the decisive factors to the success of tissue engineering strategies for bone regeneration is the appropriate design of the scaffold to guide cellular responses toward bone differentiation. The materials used for bone augmentation or repair are measured as being biocompatible, bioactive and able to undergo total degradation without toxic residues. Also, it is expected that over time bone tissue will replace the grafted materials.
The most suitable synthetic bone graft that is currently available to clinicians is osteoconductive or having bone-bonding properties, rather than being bioactive. The general opinion, however, is that these synthetic bone grafts only passively support bone formation and generally do not induce bone formation. Bone regeneration still remains a challenge in tissue engineering; different approaches, based either on bone grafts, or on artificial materials, such as ceramics, hydroxyapatite-based products and polymers, are widely investigated.
In bone replacement, bioactive materials can form intimate bonds with a bone tissue. They are used alone, as carriers for growth factors, as coatings on metallic implants, and as tissue-engineering scaffolds. It has been shown that most of these materials are biocompatible rather than bioactive, namely having no inherent biological activity. In clinical applications of tissue engineered bone regeneration, a material must be identified that can fulfill the pragmatic functions of a scaffold and carrier. Furthermore, the material should facilitate mesenchymal adult stem cells (MCs) differentiation along the osteoblastic pathway. Whether or not the physiology of cells is differently affected by adhesion to these inorganic surfaces is not known; however, adhesion-mediated changes in gene transcription may be responsible for osteogenesis on one scaffold but not on another. Besides the composition of material, another important variable to consider when predicting the eventual fate of the MCs is the interaction between the MCs and their physical properties, such as topography and stiffness.
Natural coral bone graft substitutes (BGS) are derived from the exoskeleton of marine madreporic corals. Natural coral (Porites) consists of a mineral phase, principally calcium carbonate in the structural form of aragonite with impurities, such as Sr, Mg and F ions, and an organic matrix. Researchers first started evaluating corals as potential bone graft substitutes in the early 1970s in animals and in 1979 in humans. The structure of the commonly used coral, Porites, is similar to that of cancellous bone and its initial mechanical properties resemble those of bone. Commercially available coral (Biocoral™) is used as a bone graft material and has been reported to be biocompatible and resorbable [4,5]. This biomaterial is also osteoconductive and resorbable, resulting in the complete regeneration of bone tissue within 6 months, as shown by radiographic follow-up analysis [1,4,5]. Coral has also been used clinically with good results in spinal fusion [5,6], cranial surgery [7] or to fill periodontal defects. Coral-derived material described as coralline HA is also commercially-available (Pro Osteon®, Interpore Cross). It is prepared by hydrothermally converting the original calcium carbonate of the coral Porites in the presence of ammonium phosphate [8]. This hydrothermal process maintains the original interconnected macroporosity of the coral. Coralline HA was identified as a core carbonated hydroxyapatite (CHA) on inner CaCO3 struts. As a result of this heterogeneity, coralline HA dissolves and reacts inconsistently in vivo. Highly porous calcium phosphate ceramics can also be obtained from porous-apatite of lime-encrusted ocean algae (Frios® Algipore®). The manufacturing process retains the pure mineral framework of the algae, leaving an interconnected porous structure and a rough surface. It has been shown that the biomaterial is resorbed slowly and substituted by the host bone [9].
The exoskeleton of these high content calcium carbonate scaffolds has since been shown to be biocompatible, osteoconductive, and biodegradable at variable rates depending on the exoskeleton porosity, the implantation site and the species. Although not osteoinductive or osteogenic, coral grafts act as an adequate carrier for growth factors and allow cell attachment, growth, spreading and differentiation[2,9]. When applied appropriately and when selected to match the resorption rate with the bone formation rate of the implantation site, natural coral exoskeletons have been found to be impressive bone graft substitutes.
Bioactive bone substitutes that have been used as bone replacement materials are based on SiO2 incorporated into CaO and MgO bioceramics, also termed bioglass. Kokubo proposed that Si ions are gradually released from the biomaterial [10]. Carlisle et al. found that Si plays a critical role for generation of bone tissue. The newly formed bone always contains about 0.5% of Si [11].
By itself, pure hydroxyapatite (HA) mineral is a poor bone substitute [12]. Mineral bone substitute that consists of tricalcium phosphate and HA (40:60%) was found to be optimal as a biocompatible biomaterial [13].
U.S. Pat. No. 7,008,450 [14] discloses a method of affecting the coral surface by coating coral with silicium, magnesium and phosphate by a hydrothermic procedure to get a surface of hydroxyapatite with 0.6 wt % of silicium.